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Antipsychotics possessing antidepressive efficacy increase Golf protein in rat striatum

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Abstract

Introduction

Recently, second-generation antipsychotics (SGAs) have been widely used in the treatment of mood disorders. However, the mechanisms of the antidepressant effect of SGAs remain unclear. We proposed that Golf protein, a stimulant α-subunit of G protein coupled with the dopamine D1 receptor, might a play the key role in the antidepressive effect of antidepressants. To clarify the relationship between Golf protein and the antidepressive effects of antipsychotics, we examined the effects of chronic treatment with several antipsychotics on the level of Golf protein in the rat striatum.

Materials and methods

Male Wistar rats were treated with one of several antipsychotics for 2 weeks: olanzapine (2, 5, or 10 mg/kg), sulpiride (5, 10, or 50 mg/kg), amisulpride (3, 10, or 20 mg/kg), risperidone (0.2 or 2 mg/kg), haloperidol (0.3 or 3 mg/kg), or clozapine (2 or 10 mg/kg).

Results and discussion

Olanzapine (5 mg/kg), sulpiride (5, or 10 mg/kg), and amisulpride (10 mg/kg) treatments significantly increased the level of Golf protein, but there was no increase with administration of higher doses of these three antipsychotics. Risperidone, haloperidol, and clozapine treatment did not change the level of Golf protein at any dose. In this study, all antipsychotics that have antidepressive effects increased Golf protein. This suggests that an increase in Golf may play an important role in the antidepressive effect of antipsychotics.

Conclusion

We postulate that the increase in Golf protein levels result in an increase the proportion of D1 receptors in the high-affinity state and that augmentation of the dopaminergic system exerts the antidepressant effect.

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Acknowledgements

This study was supported by research grants from the Zikei Institute of Psychiatry.

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Authors and Affiliations

  1. Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan

    Hideki Taoka, Takeshi Ishihara & Shigetoshi Kuroda

  2. Kasaoka Hospital, 2543 Imadate, Kasaoka, 714-0022, Japan

    Hideki Taoka

  3. Department of Neuropsychiatry, Hamamura Clinic, 5-1-17 Ogawa Kojima, Kurashiki, 711-0911, Japan

    Takashi Hamamura

  4. Fujisawa Hospital, 383 Kozuka, Fujisawa, 251-8530, Japan

    Shiro Endo

  5. Okayama Red Cross General Hospital, 2-1-1 Aoe, Okayama, 700-0941, Japan

    Shinji Miyata

  6. Graduate Clinical Training Center of Okayama University Hospital, 2-5-1, Shikata, Okayama, 700-8558, Japan

    Kishio Toma

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  1. Hideki Taoka
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  2. Takashi Hamamura
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Correspondence to Takashi Hamamura.

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Taoka, H., Hamamura, T., Endo, S. et al. Antipsychotics possessing antidepressive efficacy increase Golf protein in rat striatum. Psychopharmacology 201, 229–235 (2008). https://doi.org/10.1007/s00213-008-1264-y

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